Osteoclasts arise from hematopoietic stem cells and are the primary cells responsible for physiological and pathological bone resorption. Changes in the levels of cytokines and growth factors in bone microenvironment cause abnormal bone resorption by the osteoclasts (for a review see Mundy, et al., 1997). Accordingly, forced expression of IL-4 (Lewis, et al., 1993), and G-CSF (Takahashi, et al., 1996) in mice induced osteopenia, while mice overexpressing soluble TNF-.alpha. receptor (Ammann, et al., 1997) or depleted of the IL-6 gene (Poli, et al., 1994) are protected against bone loss caused by estrogen deficiency. Recent studies have demonstrated that OPGL is an essential and sufficient regulator of osteoclast differentiation, activity and survival (Kong, et al., 1999).